Welcome to our SMID Cap conference. My name is Yatin Suneja. I am one of the biotech analysts here at Guggenheim. It is my pleasure to welcome our next presenting company, Adicet. We have a few executives from the company here in the room, but I will be chatting with the President and CEO, Chen Schor, who is here with me. Chen, why don't you make some opening comments? Tell us about Adicet, and, you know, specifically about your gamma delta T cell program. Some announcement you made today, which was pretty timely in my view, so sort of touch on that, and then we'll go into sort of a Q&A discussion.
Absolutely. Good afternoon, and thank you, Yatin, for inviting us. Always a pleasure to talk to you. Adicet is the leading company in the field of gamma delta T cell therapy. The benefit of gamma delta T cells are a few. One, these are completely off-the-shelf allogeneic cell therapies that we can dose. Two, they expand just like alpha beta T cells. If you look at the Cmax of gamma delta T cells, specifically, ADI-001, the Cmax is consistent with autologous cell therapies. The day 28 is overall consistent with autologous cell therapies. Very nice exposure, just like autologous cell therapies. Yet safety seems to be favorable compared to autologous cell therapies. The key difference: autologous cell therapies are associated with this high frequency and high grade of CRS and ICANS. It's primarily due to the activation profile of alpha beta T cells.
Gamma delta T cells have different activation profile and are not associated with that high CRS and ICANS and the high frequency of high grade, CRS and ICANS, so potentially safer. Gamma delta T cells have very strong tropism to tissues, like lymph nodes or kidneys or lungs, and we can expand on this later. Overall, off-the-shelf, potentially safer, very high exposure in the blood and in the lymph nodes, and can benefit patients either with autoimmune diseases or in oncology. In oncology, there's another benefit, and that benefit is innate anti-tumor activity provided by the gamma delta 1 T cells. Today, we did provide an update on enrollment. We went into a conference. We knew that a lot of the questions will be focused on enrollment, and it's going great.
We started enrolling in November, both in autoimmune patients, you know, over two months and, you know, a couple more days. We enrolled three patients and the same in oncology. In both programs, there's a lot of interest, and patients essentially are lined up to the next dose levels.
Very good. Thank you for that sort of update. Maybe one more high-level question. You know, this is specifically on the antigen of choice. You know, there has been a fair amount of debate between CD19, CD20. Just help me understand the benefit. Like, why did you prefer to go with CD20? What are the benefits of it? Do we need a CD19?
Sure, absolutely. CD19 and CD20 have a lot of overlap in terms of their presentation on B cells. CD20 is a little more stable in its expression on the B cells. The bottom line, we actually have clinical data that show that it actually doesn't matter between CD19 and CD20. Two important points of data. One, in the blood. We have shown, we published a data set from 24 patients. In 23 out of the 24 patients, we completely depleted CD19 B cells in the blood. That doesn't mean anything, by the way, because also Rituximab does that.
I see.
The key is in the lymph nodes because it's been published that what you need in order to provide this immune reset is really to deplete the CD19 B cells both in the blood and in the lymph nodes. Cell therapies, you know, such as has been tested so far where they did show the data, those that show overall durable responses did deplete CD19 B cells in the lymph nodes, and antibodies like Rituximab and others do not deplete CD19-positive B cells in the lymph nodes. What is important in our case, we completely depleted CD19 B cells in the lymph node, and we completely depleted CD19 B cells both in the blood, I'm sorry, and in the lymph nodes. In all the biopsies that we took at day 10 in lymphoma, when we looked for, for CD19 B cells, we do not find them.
Zero.
Okay. Interesting. One more, high-level question. With regard to the gamma delta T cell versus the other CAR T cell approach, what about the durability? What do we know from cancer, you know, if you achieve a complete remission, let's say, with, you know, alpha beta versus gamma delta? The durability similar for both approaches, or is it different?
I would say that oncology might, might not be a good predictor.
Okay.
First of all, I'll describe our data in oncology, and then I'll say why I don't think it's a good predictor. In DLBCL, our durability was subpar to the autologous cell therapies. Granted, 50% of the patients progressed on autologous cell therapies, and we know that's a very tough patient population. In MCL, which is a little less aggressive tumor, our durability was actually exactly the same as autologous.
I see.
The median durability of complete response was 17.5 months, exactly what's on the label of the autologous cell therapies. That's not a good predictor for autoimmune. The reason is persistence of the cells. Autologous cell therapies, if you look at data from Novartis, Bristol Myers Squibb, Schett, no matter what data set you look at, the autologous CAR T go in, they deplete, and between day 30 to day 60, they disappear from the system.
Yeah.
There is no need for persistence. Our gamma delta T cells, and specifically ADI-001, depends on the dose level. They persist in the blood, up to 90 days.
Okay.
I would expect that the PK that we see is overall consistent with the PK of autologous cell therapies in autoimmune.
Very good. Very interesting. Okay. Going on to your program, right, the autoimmune program for ADI-001, could you just talk about the study design, the doses that you're using, at least for these first three lupus patients, what type of patient you are able to enroll, and then when you have the data later this year in the first half, at least, like, what would be the expectations?
Absolutely. So indeed, we're currently enrolling only lupus nephritis patients. We expect enrollment this quarter to systemic lupus, to systemic sclerosis, and to myositis, and in the second half of this year, also to ANCA vasculitis. We'll have data in the first half of this year in lupus nephritis, and in the second half of this year for the other indications, primarily LN, and systemic sclerosis and myositis. The study design is quite, quite the same. The starting dose level is a 3 8.
38.
The second dose level is 1 9. It's conditioning, standard conditioning, consistent with what Kyverna has tried, and then a single dose of ADI-001. Then we measure the relevant disease score, depends on the autoimmune indication and the relevant biomarkers. Specifically in lupus nephritis, we'll have data about kidney function, eGFR, proteinuria. We'll have data about the disease score, SLEDAI. We'll have data about B cell depletion in the blood, and we know that if we deplete in the blood, we deplete in the lymph nodes. We have a lot of data about that. We'll have whatever biomarker data we're able to assemble at the time that we disclose. It's gonna be pretty data-rich, and the trial is enrolling well so far.
Got it. In the first half, like, do I mean, you can only enroll one or dose one patient per month, right? How many patient worth of data you or we should anticipate, and is there a minimum follow-up that you would want to have on each patient before you disclose the data?
What we've heard, so we haven't got exactly how many patients, but, you know, three patients in two months or two months and a couple of days, you can extrapolate. It depends when we disclose. You know, talking to investors, what we've heard is that they wanna see a couple of patients at the three months.
Yeah.
We would expect to have it. The reason they wanna see a couple of patients three months is because we all know that per se those cell therapies are out of the system way before the three months, and overall, the disease improves in the first three months, and then there might be there is continued improvement, but it's not huge between three months and beyond. If we have a few patients and we show nice efficacy at the three months, that's a big win because that's consistent with autologous cell therapies, and both therapies don't have the CAR T in the system by that point.
Got it. Got it. Okay. Okay. And then you've not only enrolled, but you have dosed these patients, right? At least these three patients. What is your view about disclosing on, you know, the safety side? If we do not hear from you anything, it sort of is a good thing, right? You're not seeing anything? Just curious about the disclosure on the safety side.
you know, we didn't think about disclosure on the safety side because we're not concerned about safety.
CRS.
We had patients that asked if they got placebo. We're really not concerned about safety. Yeah. We never actually asked that question.
Okay. Very good. You feel pretty good about the safety.
Yeah.
In other words, now, after these three patients, you move to the next dose, or it's six patients per dose compartment?
Yes. The starting dose level is 3 9. Sorry, 3 8. The plan is to go to 1 9. Actually, some of the patients that were enrolled were enrolled at a lower dose of 1 8 because initially, we thought about starting with the 1 8, then we changed the protocol to 3 8, but some of the sites have not cleared that amendment. Some of those patients will be at 1 8. Yes, now we are enrolling at 3 8, and then we will enroll at 1 9.
I see. So you're not at nine yet.
We're not at 1 9 yet.
Okay. Okay. Is it, like, particular now? Is it three patients per cohort?
Yes.
You go up?
Yes.
Okay. Very good. Very good then. What about, you know, the other cohorts? Like, when do you anticipate, sort of start, getting data from other two cohorts, and how should we think about the enrollment there?
Sure. We expect to open, for enrollment, later in the quarter, for systemic sclerosis and myositis. And then it usually takes a little bit to get the first patient.
Yeah.
There is certainly interest in both indications, and we'll have to see. Obviously, we have a forecast of enrollment, but we'll have to see, and we may or may not provide some update about these cohorts once we enroll.
We get the data.
Yeah.
Okay. You feel pretty good about the safety, right? You do have a lower risk of both CRS and ICANS. Do you consider an opportunity to increase the dose, and maybe adopt a lymphodepletion-free approach that some of the other companies are trying to do? Would that be even feasible?
Yeah, that's a great question. So far, we haven't, we haven't seen the need to increase beyond 1 9. We haven't seen any pushbacks from investigators on the cyclophosphamide, fludarabine regimen. I know that it's a question that,
Yeah.
A lot of investors are asking. It's funny. Two years ago, investigators were asking about it. Now they don't.
Okay.
Because they're used to cyclophosphamide in their practice, so that's nothing new. They're used to nucleoside analogs. So fludarabine is essentially a slightly different version of that. And when they look at the potential benefit, you know, even if 50% of their patients have durable CR, that sounds amazing for them.
Yeah.
No pushback. We are planning to test without fludarabine at some point, and we will update on our plans in the near future.
Okay.
We do expect to.
Okay. These initial patients that you are able to get, the lupus patient, like, what type of patients are these, I mean, you know, obviously, Schett was able to enroll a lot younger patient, maybe a little more healthier than you can find in clinical studies these days. I am curious if you can articulate for us the type of patient that you are seeing and what is FDA allowing you to do.
These are lupus nephritis patients. You know, usually, they try a couple of therapies, you know, probably not that different from some of the other industry-sponsored studies, not necessarily the ISTs.
Yeah. Okay. So general patient. What else? Anything else on the immunology side, at least on these studies that we should?
I'll just summarize that we're very optimistic about this program. In terms of safety, this program has generated great safety profiles so far, better than alpha beta and bispecifics . CD19 B cell depletion, we know that we can deplete both in the blood and, more importantly, in the lymph nodes, and it's a very, very large therapeutic area, and we expect to have six indications in development this year. So far, so good.
Very good. Just moving on to the commercial side, I mean, do you have thoughts on how you would think about running a pivotal study? That is one. The second question is there has been some focus on these T cell engagers. Just curious to understand the commercial dynamic, assuming you and them, they are both out there in the market, who gets T, who gets, you know, your drug first versus a TCE.
Yeah. I think it's a great question. I, so that's, now let's just talk about facts. There's some data with T cell engagers that, so some show some efficacy. Not a lot of data supporting durability. In fact, there's some data that suggests that you need some chronic dosing. The question is, what chronic dosing? That's fact number one. Fact number two, we know that bispecifics in oncology require chronic dosing. Essentially, it's chronic depletion of B cells that is, there's nothing we can do about it, is associated with infections. If we talk to oncologists that treat NHL patients with rituximab, ask them what happened to their patients during COVID-19.
Yeah.
It's not a great picture. I do think there is room both for cell therapies and for bispecifics here. Some patients who are okay to go on a new class of immunosuppressants and chronically deplete their B cells might take the bispecifics . Some patients wanna take one-time cell therapy and have pretty good chance to have essentially a complete resolution of their disease. Yeah, they might get infected with a virus that will trigger this again because they're genetically predisposed to it, but there is a chance for a complete cure. I do think there is room for both of them. I think that we're actually in a great position because of our safety, because we should be able to dose in community settings, and, you know, that's a very convenient therapy.
I do think we have an advantage there, but there's probably room for both of them, just like in oncology. Just like in oncology, generally, if a patient can get access to a cell therapy versus a B specific, you know, I think we know what's happening. Look at the cells of the bispecifics in oncology compared to cell therapies.
Yeah. Very interesting. Okay. Then moving on to your oncology program, ADI-270, could you just tell us what that program is? I think it is our understanding that we're gonna have some RCC data in first half. What we should be looking at, how many patients, what type of patients?
Sure. Absolutely. Maybe I can describe a little bit the program. There is data to suggest that CD70 is a good target for a couple of indications. RCC is one of the important ones. Why? Because 80% of the patients with clear cell RCC have CD70 on their tumor. There is data by some of the alpha beta T cell companies that suggest that you can see a response in these patients. Patients with RCC, unfortunately, once they progress on a PD-1 and a VEGF inhibitor, and now in this country, actually, 60% of those patients take it in first line. Both of them. Once they progress, there is very little that you can do for these patients. The next best alternative has an overall response rate of about 20% and a PFS of a little more than five months.
There is really very little you can do once you progress on these two therapies. What's nice about ADI-270 is, one, the way we engage the tumor is using CD27, which is the natural receptor for CD70. It requires a pretty low threshold of CD70 presentation on the tumor cell to show efficacy. CD27 is another costimulatory domain. It is a more potent killer of those cancer cells, and it requires a lower threshold of CD70. Another advantage of CD27, what rejects gamma delta 1 T cells once we infuse them to patients is primarily the T cells. The activated T cells express CD70, so you fight back the rejection. I would expect potentially higher Cmax and better persistence. Gamma delta 1 T cells have innate tumor activity.
We actually have data to show that our product compared to alpha beta T cells with targeting CD70 for tumor cells, that where you knock down the CD70, we continue to show activity, and other alpha beta CD70-like type of products do not show this type of activity. We have TGF-beta dominant negative receptor on these, on the cells. We started enrolling patients. We enrolled three patients. We expect to continue to enroll patients. There is a lot of interest in the study. More patients are interested in slots available. We will have data in the first half of this year and in the second half of this year.
Got it. One more ques, so I have a question on the manufacturing side. You know, obviously, it's an allo approach, so, better from the COGS perspective. Also, talk about how quickly you are able to dose a patient versus some of the allo, some of the auto players, because auto, my understanding, is that wait time, wait time, at least on the autoimmune side, is still very long, and it takes them a lot longer. Just articulate for us, like, how beneficial it is to go with an allo approach.
Sure. It takes about 10 minutes to go down the elevator with the cells and about 30 minutes to thaw the cells, and then you can dose the patient. There is absolutely no issue. These are off the shelf, available. You store them, and then you lymphodeplete the patient for five days, and you can just dose them. It is really available and really convenient for the sites to use these cells. In terms of safety, they haven't shown, you know, it's not that the patient, oh my God, immediately developed grade 4 CRS or ICANS. They are really well tolerated. From that perspective, they are really off the shelf. From a COGS perspective, you know, we have an answer that we would expect COGS, COGS well below 20% of the price.
When people ask us, "What price are you having in mind?" we're saying it doesn't matter if the price of, you know, good, antibody or cell therapy, 20% takes a lot of, is very conservative when you say below 20%. COGS is really not an issue here.
Okay. Very good. What about the financials? How are the finances looking? How much is the cash runway, bond rate?
Sure. We're well funded. We raised money last year. We're funded into the second half of 2026. By then, we'll have multiple data points in lupus nephritis, in systemic sclerosis, myositis, potentially ANCA-associated vasculitis, and RCC. We're in a great, great position from that perspective.
Very good. You know, two data sets coming up in the next few months and then a lot later this year. Catalysts, a lot of catalysts this year.
Yeah. We're excited.
Thank you again.
Thank you.
Thank you so much for your time.
Thank you, guys.